Arachidonic acid metabolites and the gastro-intestinal toxicity of anti-inflammatory agents.
The relationship between gastro-intestinal damage and the inhibition of cyclo-oxygenase by non-steroid anti-inflammatory drugs is discussed. In anti-inflammatory doses, aspirin and the newer substitutes, indomethacin, ketoprofen, naproxen and flurbiprofen, which reduce prostaglandin levels in inflammatory exudates likewise inhibit cyclo-oxygenase activity in the gastric mucosa. These compounds all induce gastric damage. In contrast, sodium salicylate and a novel compound BW755C inhibit prostaglandin production in the inflammatory exudate, yet fail to inhibit gastric cyclo-oxygenase in the mucosa and do not form gastric erosions. Studies on the duration of cyclo-oxygenase inhibition with indomethacin indicate a close correlation between the rate of healing of gastric erosions and the recovery of cyclo-oxygenase activity in the gastric mucosa. No such relationship is seen in the small-intestine. The hydroperoxy metabolites of arachidonic acid, formed by the lipoxygenase enzymes, have vasodilator actions in the gastric circulation and the possible roles of lipoxygenase products in the gastric mucosa and their relationship to gastro-intestinal damage are discussed.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004064:Digestive System / Q000187:drug effects / Q000473:pathology*; D005480:Flurbiprofen / Q000494:pharmacology; D005753:Gastric Mucosa / Q000201:enzymology; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology; D007660:Ketoprofen / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D009288:Naproxen; D005480:Flurbiprofen; D007660:Ketoprofen; D001241:Aspirin; D007213:Indomethacin